Elucidation of genomic origin of synchronous endometrial and ovarian cancer (SEO) by genomic and microsatellite analysis

Ikuko Sakamoto; Yosuke Hirotsu; Kenji Amemiya; Takahiro Nozaki; Hitoshi Mochizuki; Masao Omata

doi:https://doi.org/10.3802/jgo.2023.34.e6

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자료유형: 학술저널

저자정보: Ikuko Sakamoto (Yamanashi Central Hospital) Yosuke Hirotsu (Yamanashi Central Hospital) Kenji Amemiya (Yamanashi Central Hospital) Takahiro Nozaki (Yamanashi Central Hospital) Hitoshi Mochizuki (Yamanashi Central Hospital) Masao Omata (Yamanashi Central Hospital)

저널정보: 대한부인종양학회 Journal of Gynecologic Oncology Journal of Gynecologic Oncology Vol.34 No.1

발행연도: 2023.1

수록면: 1 - 12 (12page)

DOI: https://doi.org/10.3802/jgo.2023.34.e6

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Objective: Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). Methods: We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samplesfrom 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by genesequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay andimmunohistochemical (IHC) staining of 4 repair genes. Results: Sixteen of 17 patients had at least 2 or more trunk mutations shared betweenendometrial and ovarian cancer suggesting the identical clonal origins. The shared trunkmutation are frequently found in endometrial cancer of the uterus, suggesting the uterineprimar y. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency andMSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissuewas deficient MMR and MSI-H in the whole specimen. This indicated that MMR proteindeficiency could occur during the progression of disease. Conclusion: Most SEOs are likely to be a single tumor with metastasis instead of doubleprimaries, and their origin could be endometrium. In addition, SEOs have a high frequency ofMMR gene abnormalities. These findings not only can support the notion of uterine primar y,but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.

#Keywords: Endometrial Carcinoma #Neoplasms #Epithelial Ovarian Cancer #Synchronous Multiple Primar y #Molecular Genetics

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